Involvement of calpain isoforms in ischemia-reperfusion injury in rat retina

Abstract

These results suggest that calpain isoforms may play an important role in neuronal cell death induced by retinal ischemia-reperfusion injury in rat.

Structure−Activity Relationship Study and Drug Profile ofN-(4-Fluorophenylsulfonyl)-l-valyl-l-leucinal (SJA6017) as a Potent Calpain Inhibitor

“…8 was less toxic and had no activity on both P450 induction and inhibition, but Caco-2 permeability was poor and protein binding was relatively high. However, several previously reported in vivo studies regarding 8 have shown amelioration of cataract formation, 20 protection on ischemia-reperfusion injury in retina, 21 and protection on functional recovery after delayed administration in diffuse head injury. 22 Although 8 was the best candidate compound for clinically therapeutic use, there are problems remaining such as bioavailability or protein binding that need to be overcome by pharmaceutical formulation techniques or structural modifications.…”

Spectrin and calpain: a ‘target’ and a ‘sniper’ in the pathology of neuronal cells

“…Development of specific biomarkers provides researchers and physicians with powerful tools for diagnosing injuries and their further monitoring, as well as guiding appropriate administration of therapeutic compounds. Calpain inhibitors have been shown to have significant neuroprotective properties in models of both ischemia [78,[105][106][107][108][109] and traumatic injury [110][111][112][113]. However, there is no mechanistic explanation for the effects of calpain inhibitors, as they do not reveal sufficient specifity and may act on cathepsins or on proteasomes.…”

“…Remarkably, casein zymography and changes in expression levels of calpain mRNA implicated involvement of both conventional calpains in ischemic neurodegeneration [78]. Extensive research efforts have focused on cerebral ischemia, which as a result of strokes and cardiac arrest, usually leads to death and is the main cause of disability.…”

“…In neurological events associated with ischemia, calpain appeared to be one of the major contributors to injury [76][77][78]. Remarkably, casein zymography and changes in expression levels of calpain mRNA implicated involvement of both conventional calpains in ischemic neurodegeneration [78].…”

Contribution of Calpain to Cellular Damage in Human Retinal Pigment Epithelial Cells Cultured with Zinc Chelator

“…16−18 Our previous studies suggested that calpains play important roles in retinal cell death induced by hypoxia in vitro 19,20 and in ischemia-reperfusion injury in vivo. 21 Recent reports also showed involvement of calpain isoforms in a spontaneous retinal degeneration model, in the WBN/Kob rat, 22 and in cultured photoreceptor cell damage. 23 To our knowledge, the involvement of calpains in RPE cellular damage has not been studied.…”